1. Cell & Tissue Renewal Lecture 39A BSCI 420,421,620Dec 4, 2002 “It’s not that I’m afraid to die, I just don’t want to be there when it happens” - Woody Allen 1.Cell and Tissue Renewal in Animals 2.Cell death - Apoptosis

2. 1.Cell and Tissue Renewal in Animals Three factors control the rate that any population of cells increases: a.The rate that cells cycle and divide b.The fraction of cells in the cell cycle (vs. G0 or out of cycle) c.The rate of cell death In multicellular animals, once the periods of embryonic and fetal development and growth are completed, most cells withdraw from the cell cycle. Adult cells can be divided into three different proliferative behaviors: (Handout) a.Renewing (continually renewed from stem cells) b.Expandable (reserve G0 cells can expand/ replace cells) c.Static (Stable, differentiated populations perm out of cycle)

3. a.Renewing (continually renewed from stem cells) What is a stem cell? 1.A dividing cell that usually produces one stem cell and one cell that goes on to become terminally differentiated. 2. It is not terminally differentiated 3. [ Text: It can divide without limit] ?

4. How does a cell produce unequal daughter cells?

5. An example of environmental asymmetry: 1.Unequal contact with a stromal cell. (activates receptors on one cell and not the other) An example of division asymmetry: 2.Unequal distribution to sister cells of cytoplasmic or nuclear proteins or RNAs (e.g., for TFs). Thus, one cell remains a stem cell while a sister cell goes forward and differentiates.

6. a.Renewing (continually renewed from stem cells) E.g. Blood cells arise from multipotent stem cells

7. 2 nd e.g. intestinal epithelial cells:

8. b.Expandable (reserve G0 cells can expand/ replace cells) Mitogens like PDGF stimulate the MAPK path and mitosis. E.g. fibrolasts, endothelial cells, and smooth muscle heal a wound. Another e.g. Satellite cells are myogenic precursor cells can Proliferate when a skeletal muscle fiber Is killed.

9. These proliferating pre-myoblasts differentiate into new Myoblasts, and fuse to form multinucleated myotubes, which develop into new muscle fibers. (DNA stained blue, myosin stained w fl. Anti-myosin)

10. c. Static (Stable, differentiated populations perm out of cycle) E.g. Neurons, skeletal and cardiac muscle cells. However, recent research has found BrdU-labeled cells in the brain that can differentiate into neurons. Similar “stem cells” found to re-populate the hippocampus, a region associated with learning.